Leishmaniasis Control in Dogs [Announcer] This program is presented by the Centers for Disease Control and Prevention. [Sarah Gregory] Hi, I’m Sarah Gregory, and today I’m talking with Dr. Domenico Otranto in Italy. Dr. Otranto is a professor of human and animal parasitic diseases in the Department of Veterinary Medicine at the University of Bari. Welcome, Dr. Otranto. [Domenico Otranto] Buongiorno Sarah. Hi! [Sarah Gregory] Hi! [Domenico Otranto] And thank you for inviting me. It’s a pleasure to be here today. [Sarah Gregory] So, let’s begin. Could you explain what leishmaniasis is? Where does it usually occur, and what are its symptoms? [Domenico Otranto] Yes, Sarah. I would say, leishmaniases, because almost 21 species of Leishmania protozoa have been isolated from humans, and they may cause cutaneous, mucocutaneous, and visceral forms of the disease. So, they represent a major burden in endemic areas, with at least 350 million people at risk in the world and approximately 1.5 million new cases each year. These infections have been known for centuries overseas, as they have been supposed to be originated in South America, about 47 to 36 millions of years ago. And just consider that cutaneous forms have been represented in potteries, “huacos,” in pre-Colombian times. And they were also well known in the Mediterranean Basin, in the Middle East as “bouton de Aleppo.” So, they are typically anthroponotic…they are typically anthroponotic Leishmania species, such as Leishmania donovani, and other zoonoses, such as Leishmania tropica, major, and infantum. The latter, Leishmania infantum, is the main agent of canine leishmaniasis, which is one of the most important vectorborne parasitic diseases of dogs, occurring on all countries except Oceania. So, their distribution is mostly tropical and subtropical. Leishmania is endemic in Eurasia, Africa, and the Americas, although I would say that Leishmania causing cutaneous lesions on macropods, like kangaroos or wallabies, has been characterized in the north of Australia. So, the epidemiology of leishmaniasis is complex, as it involves different vectors, hosts, and parasite species living in a constantly changing environment. Other factors have been relevant in the introduction and spread of the disease to regions where infections were not previously found. For example, the adoption and transportation of dogs from areas of canine leishmaniasis endemicity or the establishment of permanent sand fly vector populations in previously free areas. Which is the result…so, the result is Leishmania is expanding to new areas in Europe, northwards from the Mediterranean regions, and in the Americas, southwards, to the triple- border between Argentina, Brazil, and Paraguay, and has also reached Uruguay. So, the pathogenesis of this disease is rather complicated. Indeed, depending on the parasite tropism, amastigotes invade macrophages in the skin, mucosa, and internal organs, mostly the spleen, the liver, and bone marrow, and they cause their depletion. Accordingly, this pathogenesis I briefly summarize: clinical presentations may vary from localized skin lesions to Page 1 of 8 Leishmaniasis Control in Dogs December 2019 generalized disease, with fever, weight loss, enlargement of the spleen and liver, anemia, leukopenia, and thrombocytopenia. In dogs, the infection by Leishmania infantum may be asymptomatic. And this is quite important considering over 80% of the cases in some areas are asymptomatic or may evolve to life- threatening overt disease with a wide range of clinical signs, from localized skin alterations to severe loss of weight and generalized lymphadenomegaly. Therefore, it’s really difficult to say which are the symptoms, because the severity of the infection depends on the host’s immune system, nutritional status, but also by protozoon species by themselves and the strain, and also to a lesser extent, sand flies…by the sand fly species involved in the transmission. Yes, just a detail, this infection is transmitted by small, tiny yellowish insects also known as sand flies. [Sarah Gregory] So, how does it spread? [Domenico Otranto] So, the Leishmania protozoa are transmitted through the bites of sand flies, Phlebotominae. These are the only proven biological vectors of the parasites, although biting midges infected by Leishmania have been found in Australia. Secondary modalities of transmission in dogs may be sexual or congenital, as well as transmission by blood transfusion. In a study conducted in Madrid in human patients, the amastigotes of Leishmania infantum have also been found in macrophages from 34 to 52 percent of discarded syringes of drug addicts. And this raises the question on possible mechanical transmission among drug users. However, I would say that all these secondary modalities are of minor concern, since I would say that the only relevant transmission way for these protozoa are sand flies. [Sarah Gregory] So, what animals can get…can get it besides dogs and humans? [Domenico Otranto] In most cases, leishmaniases are zoonoses, affecting the poor in rural and natural areas where a plethora of domestic and wild reservoir hosts and sand fly vectors maintain the infection. While there is an increasing number of other mammalian hosts, like cats, rats, foxes, dogs really have…they play a major role in maintaining and transmitting the infection to other receptive hosts through the sand fly vectors. So, just consider that in disease-endemic areas, 13 out of the 21 human-infective Leishmania have also been reported in domestic dogs. However, many species of rodents, marsupials in the wild are considered hosts as alternative reservoirs of zoonotic Leishmania. For example, the reservoir of Leishmania major in the Middle East are gerbils. [Sarah Gregory] Some countries are trying to control this disease by culling dogs. Tell us about this culling. [Domenico Otranto] Yes, indeed. Dogs are regarded as the principal reservoirs of Leishmania infantum, which is so far considered the most important and spread zoonotic Leishmania species. Therefore, as far as canine leishmaniosis, the culling of seropositive dogs has long been the recommended for a control strategy in several countries, as a means to decrease the prevalence of infection in dogs, and ultimately reducing the incidence of human leishmaniasis. So, we know that the culling of animal reservoirs has been a common practice since ancient times for controlling the propagation of many diseases of zoonotic concern, not only leishmaniasis, including rabies, for example. However, the impact of this measure on disease transmission depends on the biology and virulence of the etiological agents which are…that are Page 2 of 8 Leishmaniasis Control in Dogs December 2019 involved, or on the transmission modality, direct versus vector transmission, the number…on the number of animals infected and of those that are culled, the epidemiological scenario, epidemiology versus endemic situation, and also the existence of alternative wildlife reservoirs. So, the rationale is that dogs serologically positive to Leishmania infantum are culled in order to reduce the number of infected dogs and ultimately the risk of zoonotic visceral leishmaniasis in humans, for example, in Brazil, where about 3,500 human cases of visceral leishmaniasis are reported each year. But this strategy is absolutely not successful. [Sarah Gregory] What are the ethical implications of culling? And I want to say here for listeners in case there are a few that don’t…aren’t clear that culling is euthanizing, right? Killing the dogs? [Domenico Otranto] Yes. I will say that, as a scientist, veterinarian, and as the representative of the most evolved biped animal living on our earth, I just say that we should not be killing other animals. This was the teaching of many great persons, such as San Francesco from Assisi, who left a mark in the way of thinking of the Western culture, also for non-Catholics. However, coming back to canine leishmaniosis, as veterinarians, we swear to use scientific knowledge and skills for the benefits of society through the protection of animal health and welfare, the prevention and relief of animal suffering, the conservation of animal resources, the promotion of public health, and the advancement of medical knowledge. So, specifically, an important weakness of this strategy for canine leishmaniosis could be represented by culling seropositive, but healthy, dogs which have a minimal, if not null, impact in the spreading of the infection to animals and humans. This is just unethical. Again, scientific data clearly suggest that dog culling is not a useful strategy for the control of visceral leishmaniasis by Leishmania infantum. For example, in Brazil, where it is a common practice, there has not been any reduction in the overall year number of human cases and, therefore, would be unethical to kill animals. [Sarah Gregory] Where is dog culling most commonly practiced? [Domenico Otranto] This practice is recommended officially in South America: Argentina, Brazil, Colombia, Uruguay and Venezuela; in the Mediterranean region: Morocco, Tunisia; Middle East and Central Asia: like Armenia, Azerbaijan, Iran, Iraq, Syria, Uzbekistan. But in many parts of the world where there is not an official recommendation, but it is eventually unofficially done in practice, there…dog culling is a common practice as well, like in South America: Paraguay, in Albania and Algeria in the Mediterranean area, also in Middle East and Central Asia. However, we should mention that, for a long time, dog culling strategy was applied indiscriminately to all seropositive dogs. For example, in Brazil, regardless if they were sick or subclinically infected, regardless if they were not only exposed or truly infected. Nowadays, something is changing. Owners have the right to treat their dogs, if infected and sick. So, the dog culling strategy is becoming selective… this is really important… and it has been for a long time in other countries where canine leishmaniasis is endemic. For instance, in the United States, seropositive dogs may be eliminated, but only if the owners agree.